Role of cholecystokinin in anorexia induction following oral exposure to the 8-ketotrichothecenes deoxynivalenol, 15-acetyldeoxynivalenol, 3-acetyldeoxynivalenol, fusarenon X, and nivalenol.
Cereal grain contamination by trichothecene mycotoxins is known to negatively impact human and animal health with adverse effects on food intake and growth being of particular concern. The head blight fungus Fusarium graminearum elaborates five closely related 8-ketotrichothecene congeners: (1) deoxynivalenol (DON), (2) 3-acetyldeoxynivalenol (3-ADON), (3) 15-acetyldeoxynivalenol (15-ADON), (4) fusarenon X (FX), and (5) nivalenol (NIV). While anorexia induction in mice exposed intraperitoneally to DON has been linked to plasma elevation of the satiety hormones cholecystokinin (CCK) and peptide YY₃₋₃₆ (PYY₃₋₃₆), the effects of oral gavage of DON or of other 8-keotrichothecenes on release of these gut peptides have not been established. The purpose of this study was to (1) compare the anorectic responses to the aforementioned 8-ketotrichothecenes following oral gavage at a common dose (2.5 mg/kg bw) and (2) relate these effects to changes plasma CCK and PYY₃₋₃₆ concentrations. Elevation of plasma CCK markedly corresponded to anorexia induction by DON and all other 8-ketotrichothecenes tested. Furthermore, the CCK1 receptor antagonist SR 27897 and the CCK2 receptor antagonist L-365,260 dose-dependently attenuated both CCK- and DON-induced anorexia, which was consistent with this gut satiety hormone being an important mediator of 8-ketotrichothecene-induced food refusal. In contrast to CCK, PYY₃₋₃₆ was moderately elevated by oral gavage with DON and NIV but not by 3-ADON, 15-ADON, or FX. Taken together, the results suggest that CCK plays a major role in anorexia induction following oral exposure to 8-ketotrichothecenes, whereas PYY₃₋₃₆ might play a lesser, congener-dependent role in this response.


Multiferroic Dislocations in Ferroelectric PbTiO3.
Ultrathin multiferroics with coupled ferroelectric and ferromagnetic order parameters hold promise for novel technological paradigms, such as extremely thin magnetoelectric memories. However, these ferroic orders and their functions inevitably disappear below a fundamental size limit of several nanometers. Herein, we propose a novel design strategy for nanoscale multiferroics smaller than the critical size limit by engineering the dislocations in nonmagnetic ferroelectrics, even though these lattice defects are generally believed to be detrimental. First-principles calculations demonstrate that Ti-rich PbTiO3 dislocations exhibit magnetism due to the local nonstoichiometry intrinsic to the core structures. Highly localized spin moments in conjunction with the host ferroelectricity enable these dislocations to function as atomic-scale multiferroic channels with a pronounced magnetoelectric effect that are associated with the antiferromagnetic-ferromagnetic-nonmagnetic phase transitions in response to polarization switching. The present results thus suggest a new field of dislocation (or defect) engineering for the fabrication of ultrathin magnetoelectric multiferroics and ultrahigh density electronic devices.


Pay for performance in primary care: the contribution of the Programme for Improving Access and Quality of Primary Care (PMAQ) on avoidable hospitalisations in Brazil, 2009-2018.
Evidence on the effect of pay-for-performance (P4P) schemes on provider performance is mixed in low-income and middle-income countries. Brazil introduced its first national-level P4P scheme in 2011 (PMAQ-Brazilian National Programme for Improving Primary Care Access and Quality). PMAQ is likely one of the largest P4P schemes in the world. We estimate the association between PMAQ and hospitalisations for ambulatory care sensitive conditions (ACSCs) based on a panel of 5564 municipalities. We conducted a fixed effect panel data analysis over the period of 2009-2018, controlling for coverage of primary healthcare, hospital beds per 10 000 population, education, real gross domestic product per capita and population density. The outcome is the hospitalisation rate for ACSCs among people aged 64 years and under per 10 000 population. Our exposure variable is defined as the percentage of family health teams participating in PMAQ, which captures the roll-out of PMAQ over time. We also provided several sensitivity analyses, by using alternative measures of the exposure and outcome variables, and a placebo test using transport accident hospitalisations instead of ACSCs. The results show a negative and statistically significant association between the rollout of PMAQ and ACSC rates for all age groups. An increase in PMAQ participating of one percentage point decreased the hospitalisation rate for ACSC by 0.0356 (SE 0.0123, p=0.004) per 10 000 population (aged 0-64 years). This corresponds to a reduction of approximately 60 829 hospitalisations in 2018. The impact is stronger for children under 5 years (-0.0940, SE 0.0375, p=0.012), representing a reduction of around 11 936 hospitalisations. Our placebo test shows that the association of PMAQ on the hospitalisation rate for transport accidents is not statistically significant, as expected. We find that PMAQ was associated with a modest reduction in hospitalisation for ACSCs.


Helping people with AIDS live well at home.
Responding to AIDS as a chronic, multisystem disease means emphasizing quality of life as the chief goal throughout its course. By mobilizing and supporting the strengths of the individual and his/her social network, the homecare nurse allows the person with AIDS or ARC to focus his/her energy on being well, not the disease. Meeting the challenge requires commitment, creativity, collaboration, and compassion.


LECT2 Is a Novel Antibacterial Protein in Vertebrates.
In vertebrates, leukocyte-derived chemotaxin-2 (LECT2) is an important immunoregulator with conserved chemotactic and phagocytosis-stimulating activities to leukocytes during bacterial infection. However, whether LECT2 possesses direct antibacterial activity remains unknown. In this article, we show that, unlike tetrapods with a single LECT2 gene, two LECT2 genes exist in teleost fish, named LECT2-a and LECT2-b Using grass carp as a research model, we found that the expression pattern of grass carp LECT2-a (gcLECT2-a) is more similar to that of LECT2 in tetrapods, while gcLECT2-b has evolved to be highly expressed in mucosal immune organs, including the intestine and skin. Interestingly, we found that gcLECT2-b, with conserved chemotactic and phagocytosis-stimulating activities, can also kill Gram-negative and Gram-positive bacteria directly in a membrane-dependent and a non-membrane-dependent manner, respectively. Moreover, gcLECT2-b could prevent the adherence of bacteria to epithelial cells through agglutination by targeting peptidoglycan and lipoteichoic acid. Further study revealed that gcLECT2-b can protect grass carp from Aeromonas hydrophila infection in vivo, because it significantly reduces intestinal necrosis and tissue bacterial load. More importantly, we found that LECT2 from representative tetrapods, except human, also possesses direct antibacterial activities, indicating that the direct antibacterial property of LECT2 is generally conserved in vertebrates. Taken together, to our knowledge, our study discovered a novel function of LECT2 in the antibacterial immunity of vertebrates, especially teleost fish, greatly enhancing our knowledge of this important molecule.


Mobile Exergaming for Health-Effects of a serious game application for smartphones on physical activity and exercise adherence in type 2 diabetes mellitus-study protocol for a randomized controlled trial.
Exergaming is a novel approach to increase motivation for regular physical activity (PA) among sedentary individuals such as patients with type 2 diabetes mellitus (T2DM). Because existing exergames do not offer fitness-level adjusted, individualized workouts and are normally stationary (TV bound), thus not enabling PA anywhere and at any time, we developed a smartphone-based, game-like software application (MOBIGAME) specifically designed for middle-aged T2DM patients to induce a healthier, more active lifestyle as part of successful T2DM treatment and management. In a randomized controlled trial we aim to examine whether our smartphone-based game application can lead to increases in daily PA in T2DM patients that are persistent in the mid to long term and whether these increases are greater than those in a control group. This study is designed as a randomized controlled trial. We plan to recruit a total of 42 T2DM patients [45-70 years, body mass index (BMI) ≥25 kg/m2, low daily PA, regular smartphone use]. The experimental intervention (duration 24 weeks) includes individualized multidimensional home-based exercise and daily PA promotion administered through MOBIGAME. The control intervention consists of a one-time standard lifestyle counseling including the promotion of baseline activities. The primary outcome is daily PA measured as steps per day. Secondary outcome is exercise adherence measured via the usage data from the participants' smartphones (experimental intervention) and as self-recorded exercise log entries (control intervention). We will test the hypothesis that there will be differences between the experimental and control group with respect to post-interventional daily PA (as well as all other outcomes) using analysis of covariance. For each analysis, an estimate (with 95% confidence interval) of the difference in outcome between both groups will be reported. This research will investigate the effectiveness of a novel smartphone-based, game-like software application to be used as a way to promote regular daily PA among inactive T2DM patients. The results of this trial may have important implications for future PA-promoting interventions and provide relevant information for the general transferability of such applications to be used as part of the treatment in other chronic diseases. ClinicalTrials.gov, NCT02657018 . Registered on 11 January 2016. Last status update on 3 May 2016. Kofam.ch, SNCTP-number:SNCTP000001652. Registered on 21 January 2016.


A Novel Case of an Acrochordon Occurring on the Plantar Foot.
We report on a 63-year-old male who was found to have an acrochordon on his plantar foot. Although acrochordons constitute a common benign clinical finding, this observation represents, to our knowledge, only the second case reported on the foot and the first occuring on the plantar surface.


Ultrasound-assisted Cu(I)-catalyzed azide-alkyne click cycloaddition as polymer-analogous transformation in chitosan chemistry. High antibacterial and transfection activity of novel triazol betaine chitosan derivatives and their nanoparticles.
In this work, we involved ultrasound-assisted click CuAAC in chitosan chemistry. Ultrasound-mediated CuAAC between propargylic ester of betaine and azido chitosan derivative proceeds fast in water under aerobic conditions and gives rise novel water-soluble triazole betaine chitosan derivatives. Using ionic gelation technique, we prepared and characterized nanoparticles from the synthesized chitosan derivatives. We studied antibacterial and transfection activity of the novel chitosan derivatives and their nanoparticles. The nanoparticles with size ca. 100 nm and ζ-potential ca. +65 mV proved to possess outstanding antibacterial activity, which is much more than that of the triazole betaine derivatives in their native form, and it is equal to the activity of ampicillin and gentamicin. Opposite, triazole betaine chitosan derivatives in their native form are characterized by remarkable transfection activity as compared with their nanoparticles. The most active triazole betaine chitosan derivatives are derivatives of moderate molecular weight with moderate degree of substitution. Their transfection activity is extremely high for chitosan species and it is comparable (values of the same order) with activity of Lipofectin - commercially available gene delivery vector.


Optimization of the Expression of DT386-BR2 Fusion Protein in Escherichia coli using Response Surface Methodology.
The aim of this study was to determine the best condition for the production of DT386-BR2 fusion protein, an immunotoxin consisting of catalytic and translocation domains of diphtheria toxin fused to BR2, a cancer specific cell penetrating peptide, for targeted eradication of cancer cells, in terms of the host, cultivation condition, and culture medium. Recombinant pET28a vector containing the codons optimized for the expression of the DT386-BR2 gene was transformed to different strains of Escherichia coli (E. coli BL21 DE3, E. coli Rosetta DE3 and E. coli Rosetta-gami 2 DE3), followed by the induction of expression using 1 mM IPTG. Then, the strain with the highest ability to produce recombinant protein was selected and used to determine the best expression condition using response surface methodology (RSM). Finally, the best culture medium was selected. Densitometry analysis of sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the expressed fusion protein showed that E. coli Rosetta DE3 produced the highest amounts of the recombinant fusion protein when quantified by 1 mg/ml bovine serum albumin (178.07 μg/ml). Results of RSM also showed the best condition for the production of the recombinant fusion protein was induction with 1 mM IPTG for 2 h at 37°C. Finally, it was established that terrific broth could produce higher amounts of the fusion protein when compared to other culture media. In this study, we expressed the recombinant DT386-BR2 fusion protein in large amounts by optimizing the expression host, cultivation condition, and culture medium. This fusion protein will be subjected to purification and evaluation of its cytotoxic effects in future studies.


Repair of the Orbital Wall Fractures in Rabbit Animal Model Using Nanostructured Hydroxyapatite-Based Implant.
Cellular uptake and cytotoxicity of nanostructured hydroxyapatite (nanoHAp) are dependent on its physical parameters. Therefore, an understanding of both surface chemistry and morphology of nanoHAp is needed in order to be able to anticipate its in vivo behavior. The aim of this paper is to characterize an engineered nanoHAp in terms of physico-chemical properties, biocompatibility, and its capability to reconstitute the orbital wall fractures in rabbits. NanoHAp was synthesized using a high pressure hydrothermal method and characterized by physico-chemical, structural, morphological, and optical techniques. X-ray diffraction revealed HAp crystallites of 21 nm, while Scanning Electron Microscopy (SEM) images showed spherical shapes of HAp powder. Mean particle size of HAp measured by DLS technique was 146.3 nm. Biocompatibility was estimated by the effect of HAp powder on the adhesion and proliferation of mesenchymal stem cells (MSC) in culture. The results showed that cell proliferation on powder-coated slides was between 73.4% and 98.3% of control cells (cells grown in normal culture conditions). Computed tomography analysis of the preformed nanoHAp implanted in orbital wall fractures, performed at one and two months postoperative, demonstrated the integration of the implants in the bones. In conclusion, our engineered nanoHAp is stable, biocompatible, and may be safely considered for reconstruction of orbital wall fractures.


A simple passive equilibration method for loading carboplatin into pre-formed liposomes incubated with ethanol as a temperature dependent permeability enhancer.
A passive equilibration method which relies on addition of candidate drugs to pre-formed liposomes is described as an alternative method for preparing liposome encapsulated drugs. The method is simple, rapid and applicable to liposomes prepared with high (45mol%) or low (<20mol%) levels of cholesterol. Passive equilibration is performed in 4-steps: (i) formation of liposomes, (ii) addition of the candidate drug to the liposomes in combination with a permeability enhancing agent, (iii) incubation at a temperature that facilitates diffusion of the added compound across the lipid bilayer, and (iv) quenching the enhanced membrane permeability by reduction in temperature and/or removal of the permeabilization enhancer. The method is fully exemplified here using ethanol as the permeabilization enhancer and carboplatin (CBDCA) as the drug candidate. It is demonstrated that ethanol can be added to liposomes prepared with 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and Cholesterol (Chol) (55:45mol ratio) in amounts up to 30% (v/v) with no change in liposome size, even when incubated at temperatures>60°C. Super-saturated solutions of CBDCA (40mg/mL) can be prepared at 70°C and these are stable in the presence of ethanol even when the temperature is reduced to <30°C. maximum CBDCA encapsulation is achieved within 1h after the CBDCA solution is added to pre-formed DSPC/Chol liposomes in the presence of 30% (v/v) ethanol at 60°C. When the pre-formed liposomes are mixed with ethanol (30% v/v) at or below 40°C, the encapsulation efficiency is reduced by an order of magnitude. The method was also applied to liposomes prepared from other compositions include a cholesterol free formulations (containing 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(polyethylene glycol)-2000] (DSPE-PEG2000)) and a low Chol (<20mol%) formulations prepared with the distearoyl-sn-glycero-3-phospho-(1'-rac-glycerol) DSPG)). The cytotoxic activity of CBDCA was unaffected when prepared in this manner and two of the resultant formulations exhibited good stability in vitro and in vivo. The cytotoxic activity of CBDCA was unaffected when prepared in this manner and the resultant formulations exhibited good stability in vitro and in vivo. Pharmacokinetics studies in CD-1 mice indicated that the resulting formulations increased the circulation half life of the associated CBDCA significantly (AUC0-24h of CBDCA=0.016μg·hr/mL; AUC0-24h of the DSPC/Chol CBDCA formulation=1014.0μg·hr/mL and AUC0-24h of the DSPC/DSPG/Chol CBDCA formulation=583.96μg·hr/mL). Preliminary efficacy studies in Rag-2M mice with established subcutaneous H1975 and U-251 tumors suggest that the therapeutic activity of CBDCA is improved when administered in liposomal formulations. The encapsulation method described here has not been disclosed previously and will have broad applications to drugs that would normally be encapsulated during liposome manufacturing.


Community-Academic Partnership: Intervention to Prepare Community Members for the End-of-Life Journey.
Despite research findings that rural Appalachians prefer to die at home, few people access palliative and hospice care services, and many report limited knowledge about palliative/end-of-life care resources. A community-academic partnership was formed to address this need. Train-the-trainer workshop and materials were co-developed. This study tested the feasibility and cultural acceptability of the training intervention to increase community members' knowledge about palliative/end-of-life care resources for East Tennessee Appalachian people. Community-based participatory research design and culture care theory guided the project, intervention, and research. After engaging in end-of-life training, participants completed a retrospective pretest-posttest survey. Paired samples t tests were used to compare knowledge before and after training. Means and standard deviations were used to report training material usefulness and cultural acceptability. Short-answer qualitative data were analyzed using content analysis. Sixty-six adults completed the survey. Ratings for training materials and cultural/theological acceptability were high. Participant knowledge rankings showed significant improvement after training at the P <.001 level. Qualitative feedback was positive. The training intervention was feasible, culturally acceptable, and effective for increasing East Tennessee Appalachian persons' palliative/end-of-life care knowledge. Community member expertise/collaboration integrated into every stage of the project is the bedrock of cultural acceptability and feasibility.


Reconstructing the timing and dispersion routes of HIV-1 subtype B epidemics in the Caribbean and Central America: a phylogenetic story.
The Caribbean and Central America are among the regions with highest HIV-1B prevalence worldwide. Despite of this high virus burden, little is known about the timing and the migration patterns of HIV-1B in these regions. Migration is one of the major processes shaping the genetic structure of virus populations. Thus, reconstruction of epidemiological network may contribute to understand HIV-1B evolution and reduce virus prevalence. We have investigated the spatio-temporal dynamics of the HIV-1B epidemic in The Caribbean and Central America using 1,610 HIV-1B partial pol sequences from 13 Caribbean and 5 Central American countries. Timing of HIV-1B introduction and virus evolutionary rates, as well as the spatial genetic structure of the HIV-1B populations and the virus migration patterns were inferred. Results revealed that in The Caribbean and Central America most of the HIV-1B variability was generated since the 80 s. At odds with previous data suggesting that Haiti was the origin of the epidemic in The Caribbean, our reconstruction indicated that the virus could have been disseminated from Puerto Rico and Antigua. These two countries connected two distinguishable migration areas corresponding to the (mainly Spanish-colonized) Easter and (mainly British-colonized) Western islands, which indicates that virus migration patterns are determined by geographical barriers and by the movement of human populations among culturally related countries. Similar factors shaped the migration of HIV-1B in Central America. The HIV-1B population was significantly structured according to the country of origin, and the genetic diversity in each country was associated with the virus prevalence in both regions, which suggests that virus populations evolve mainly through genetic drift. Thus, our work contributes to the understanding of HIV-1B evolution and dispersion pattern in the Americas, and its relationship with the geography of the area and the movements of human populations.


Bayesian adaptive dose-escalation designs for simultaneously estimating the optimal and maximum safe dose based on safety and efficacy.
The main purpose of dose-escalation trials is to identify the dose(s) that is/are safe and efficacious for further investigations in later studies. In this paper, we introduce dose-escalation designs that incorporate both the dose-limiting events and dose-limiting toxicities (DLTs) and indicative responses of efficacy into the procedure. A flexible nonparametric model is used for modelling the continuous efficacy responses while a logistic model is used for the binary DLTs. Escalation decisions are based on the combination of the probabilities of DLTs and expected efficacy through a gain function. On the basis of this setup, we then introduce 2 types of Bayesian adaptive dose-escalation strategies. The first type of procedures, called "single objective," aims to identify and recommend a single dose, either the maximum tolerated dose, the highest dose that is considered as safe, or the optimal dose, a safe dose that gives optimum benefit risk. The second type, called "dual objective," aims to jointly estimate both the maximum tolerated dose and the optimal dose accurately. The recommended doses obtained under these dose-escalation procedures provide information about the safety and efficacy profile of the novel drug to facilitate later studies. We evaluate different strategies via simulations based on an example constructed from a real trial on patients with type 2 diabetes, and the use of stopping rules is assessed. We find that the nonparametric model estimates the efficacy responses well for different underlying true shapes. The dual-objective designs give better results in terms of identifying the 2 real target doses compared to the single-objective designs.


Uniform culture in solid-state fermentation with fungi and its efficient enzyme production.
Solid-state fermentation (SSF) has attracted a lot of interest for carrying out high-level protein production in filamentous fungi. However, it has problems such as the fermentation heat generated during the culture in addition to the reduced mobility of substances. These conditions lead to a nonuniform state in the culture substrate and result in low reproducibility. We constructed a non-airflow box (NAB) with a moisture permeable fluoropolymer membrane, thereby making it possible to control and maintain uniform and optimal conditions in the substrate. For the NAB culture in Aspergillus oryzae, temperature and water content on/in the whole substrate were more consistent than for a traditional tray box (TB) culture. Total weight after the culture remained constant and dry conditions could be achieved during the culture. These data demonstrate the possibility of growing a uniform culture of the whole substrate for SSF. The NAB is advantageous because it allows for the control of exact temperature and water content in the substrate during the culture by allowing vapor with latent heat to dissipate out of the box. In addition, several enzymes in the NAB culture exhibited higher production levels than in the TB culture. We believe that culturing in the constructed NAB could become a standard technique for commercial SSF.


Emotional Arousal at Memory Encoding Enhanced P300 in the Concealed Information Test.
Previous studies have reported that the concealed information test (CIT) is a reliable and powerful method for detecting information. However, the external validity of the CIT studies has not been fully proven. In particular, few studies have examined the effects of emotional arousal at memory encoding on physiological responses in the CIT. The present study investigated the influence on the CIT of the magnitude of emotional arousal at memory encoding of a mock crime, using the P300 component of the event-related brain potential (ERP). In accord with the assumptions of excitation-transfer theory, we presented emotionally arousing pictures before a mock crime. Participants were randomly assigned to either a high emotional arousal group (n = 10) or a low emotional arousal group (n = 11), viewing pictures expected to arouse emotion at a high or low level, respectively. Subsequently, all participants enacted the same mock crime, in which they were instructed to stab a pillow with a sharp-edged tool (e.g., a kitchen knife or ice pick) as if harassing a mannequin lying on a bed. After the antecedent emotional experience, the P300-based CIT was conducted. Participants in the high arousal group showed significantly greater P300 amplitudes in response to a probe stimulus compared with the low arousal group. No differences were found between the groups in response to irrelevant stimuli. These results support the notion that emotional arousal influences the P300 in the CIT paradigm.


Inclusion Complexation between α-Cyclodextrin and Oligo(ethylene glycol) Methyl Ether Methacrylate.
The preparation of inclusion complexes based on α-cyclodextrin (α-CD) and oligo(ethylene glycol) methyl ether methacrylate (OEGMA) was investigated aiming to reveal complexation particularities and thermodynamic and kinetic aspects as a function of the oligomer architecture. Small-angle X-ray scattering and isothermal titration calorimetry measurements revealed that oligomer molecular weight controls both the kinetics and thermodynamics of inclusion. Unlike linear ethylene glycol polymers, OEGMA groups possess a methacrylate group, which seems to act as a stopper, affecting their mode of complexation. Nuclear magnetic resonance spectra and relaxation measurements support the fact that methacrylate groups lie outside the α-CD ring and that a full sequential complexation of the oligomer ethylene oxide groups is not observed. These results allied to the temperature sensitivity of these oligomers and enable possible routes for chemical modifications and design of new stimuli-responsive materials.


Mendelian disorders of high-density lipoprotein metabolism.
High-density lipoproteins (HDLs) are a highly heterogeneous and dynamic group of the smallest and densest lipoproteins present in the circulation. This review provides the current molecular insight into HDL metabolism led by articles describing mutations in genes that have a large affect on HDL cholesterol levels through their roles in HDL and triglyceride metabolism. Using this information from both human and animal studies, it is discussed how HDL is produced, remodeled in the circulation, affected by factors that control the metabolism of triglyceride-rich lipoproteins, how it helps maintain cellular cholesterol homeostasis, and, finally, how it is catabolized. It can be concluded that HDL cholesterol as a trait is genetically heterogeneous, with as many as 40 genes involved. In most cases, only heterozygotes of gene variants are known, and HDL cholesterol as a trait is inherited in an autosomal-dominant manner. Only 3 Mendelian disorders of HDL metabolism are currently known, which are inherited in an autosomal-recessive mode.


Combined effect of the essential oil from Chenopodium ambrosioides and antileishmanial drugs on promastigotes of Leishmania amazonensis.
To date, there are no vaccines against Leishmania, and chemotherapy remains the mainstay for the control of leishmaniasis. The drugs of choice used for leishmaniasis therapy are significantly toxic, expensive and with a growing frequency of refractory infections. Because of these limitations, a combination therapy is the better hope. This work demonstrates that the essential oil from Chenopodium ambrosioides shows a synergic activity after incubation in conjunction with pentamidine against promastigotes of Leishmania amazonensis. However, an indifferent effect has been found for combinations of meglumine antimoniate or amphotericin B and the essential oil.


Effective Enrichment and Detection of Trace Polycyclic Aromatic Hydrocarbons in Food Samples based on Magnetic Covalent Organic Framework Hybrid Microspheres.
The present study reported a facile, sensitive, and efficient method for enrichment and determination of trace polycyclic aromatic hydrocarbons (PAHs) in food samples by employing new core-shell nanostructure magnetic covalent organic framework hybrid microspheres (Fe3O4@COF-(TpBD)) as the sorbent followed by HPLC-DAD. Under mild synthetic conditions, the Fe3O4@COF-(TpBD) were prepared with the retention of colloidal nanosize, larger specific surface area, higher porosity, uniform morphology, and supermagnetism. The as-prepared materials showed an excellent adsorption ability for PAHs, and the enrichment efficiency of the Fe3O4@COF-(TpBD) could reach 99.95%. The obtained materials also had fast adsorption kinetics and realized adsorption equilibrium within 12 min. The eluent was further analyzed by HPLC-DAD, and good linearity was observed in the range of 1-100 ng/mL with the linear correlation being above 0.9990. The limits of detection (S/N = 3) and limits of quantitation (S/N = 10) for 15 PAHs were in the range of 0.83-11.7 ng/L and 2.76-39.0 ng/L, respectively. For the application, the obtained materials were employed for the enrichment of trace PAHs in food samples and exhibited superior enrichment capacity and excellent applicability.


Evaluation of two-dimensional intraoperative neuromonitoring for predicting urinary and anorectal function after rectal cancer surgery.
The aim of this study was to compare the results of two-dimensional intraoperative neuromonitoring (IONM) with the postoperative urinary and anorectal function of rectal cancer patients. A consecutive series of 35 patients undergoing low anterior resection were investigated prospectively. IONM was performed with electric stimulations of the pelvic splanchnic nerves under simultaneous manometry of the bladder and electromyography (EMG) of the internal anal sphincter (IAS). Urinary and anorectal function were evaluated preoperatively and at follow-up by standardized questionnaires, digital rectal examination scoring system, and long-term catheterization rate. The rate of postoperative newly developed bladder dysfunction was 17 %. IONM with bladder manometry had a sensitivity of 100 %, specificity of 96 %, positive predictive value of 83 %, negative predictive value of 100 %, and overall accuracy of 97 %, respectively. The proportion of patients with severely impaired anorectal function at follow-up was 8 %. The sensitivity, specificity, and positive and negative predictive values for IONM with EMG of the IAS were, respectively, 100, 96, 67, and 100 % with an accuracy of 96 %. The degree of agreement for IONM with EMG of the IAS was good for anorectal function (к = 0.780) and poor for urinary function (к = 0.119). IONM with bladder manometry yielded a very good degree of agreement for urinary function (к = 0.891) and a fair agreement for anorectal function (к = 0.336). The two-dimensional IONM method is suitable for verification of bladder and IAS innervation. Accurate prediction of urinary and anorectal function necessitates both bladder manometry and EMG of the IAS.


Processed pseudogenes in Drosophila.
Two species of Drosophila, D. yakuba and D. teissieri, possess pseudogenes of Adh. These pseudogenes lack introns and map to chromosome arm 3R, rather than to chromosome arm 2L, wherein are located the functional Adh genes. Their structure suggests that the pseudogenes arose from reverse transcripts. Because the pseudogenes map to homologous sites in both species, they presumably arose before these species diverged. Remarkably, the pattern of base substitution in the pseudogenes differs between sites that correspond to degenerate and non-degenerate codon positions in their functional paralogs.


Distinct Roles of Mitochondrial HIGD1A and HIGD2A in Respiratory Complex and Supercomplex Biogenesis.
The mitochondrial respiratory chain enzymes are organized as individual complexes and supercomplexes, whose biogenesis remains to be fully understood. To disclose the role of the human Hypoxia Inducible Gene Domain family proteins HIGD1A and HIGD2A in these processes, we generate and characterize HIGD-knockout (KO) cell lines. We show that HIGD2A controls and coordinates the modular assembly of isolated and supercomplexed complex IV (CIV) by acting on the COX3 assembly module. In contrast, HIGD1A regulates CIII and CIII-containing supercomplex biogenesis by supporting the incorporation of UQCRFS1. HIGD1A also clusters with COX4-1 and COX5A CIV subunits and, when overexpressed, suppresses the CIV biogenesis defect of HIGD2A-KO cells. We conclude that HIGD1A and HIGD2A have both independent and overlapping functions in the biogenesis of respiratory complexes and supercomplexes. Our data illuminate the existence of multiple pathways to assemble these structures by dynamic HIGD-mediated CIV biogenesis, potentially to adapt to changing environmental and nutritional conditions.


The growth rate of Mycobacterium smegmatis depends on sufficient porin-mediated influx of nutrients.
Mycobacteria have a unique outer membrane (OM) that is thicker than any other known biological membrane. Nutrients cross this permeability barrier by diffusion through porins. MspA is the major porin of Mycobacterium smegmatis. In this study we showed that three paralogues of MspA, namely MspB, MspC and MspD are also porins. However, only the mspA and mspC genes were expressed in the wild-type strain. None of the single deletion mutants displayed a significant OM permeability defect except for the mspA mutant. Deletion of the mspA gene caused activation of transcription of mspB and/or mspD in three independent strains by unknown chromosomal mutations. It is concluded that mspB and mspD provide backup porins for M. smegmatis. This also indicated that a minimal porin-mediated OM permeability is essential for survival of M. smegmatis. Electron microscopy in combination with quantitative image analysis of protein gels revealed that the number of pores per cell dropped from 2400 to 800 and 150 for the DeltamspA and DeltamspA DeltamspC mutant (ML10) respectively. The very low number of pores correlated well with the at least 20-fold lower channel activity of detergent extracts of the ML10 strain and its 15- and 75-fold lower permeability to nutrient molecules such as serine and glucose respectively. The amount of Msp porin and the OM permeability of the triple porin mutant lacking mspA, mspC and mspD was not altered. The growth rate of M. smegmatis dropped drastically with its porin-mediated OM permeability in contrast to porin mutants of Escherichia coli. These results show that porin-mediated influx of nutrients is a major determinant of the growth rate of M. smegmatis.


Functional expression in Aspergillus oryzae of p15, a protein with potent neurite-inducing activity in PC12 cells.
We previously reported that a fungal protein, p15, induces neurite outgrowth and differentiation of rat pheochromocytoma PC12 cells through the activation of the Ca2+ signaling pathway. We report here the secretory production of p15 in Aspergillus oryzae. Analysis of culture supernatant of A. oryzae transformed with the gene encoding the p15 precursor tagged with a hemagglutinin (HA) epitope demonstrated that the transformant secreted a protein with an apparent molecular mass of 17.5 kDa, which is a little larger than the expected size of mature p15-HA. By heat denaturation and ion exchange chromatography, p15-HA was easily purified from the culture supernatant with sufficient abundance. Although purified p15-HA was less active than the native p15 obtained from the culture broth of a producing fungal strain, it had neurite-inducing activity in PC12 cells in a dose-dependent manner, providing a system to study the action mechanism of p15.


Rapid tranquillisation: time for a reappraisal of options for parenteral therapy.
When parenteral treatments are indicated for acutely disturbed behaviour, previous guidelines have recommended droperidol or haloperidol in combination with benzodiazepines. However, there has been recent concern over cardiotoxicity and sudden death associated with some antipsychotic medication and droperidol has now been withdrawn. To ascertain what alternatives can be recommended to replace intramuscular droperidol. Selective review of current guidelines and the literature pertaining to rapid parenteral tranquillisation. Current guidelines recommend haloperidol as an alternative to droperidol. There is evidence of cardiotoxicity with haloperidol and it has a propensity to cause extrapyramidal side-effects that may exacerbate disturbed behaviour and reduce longer-term compliance. The rapid-acting intramuscular formulations of atypical antipsychotic agents show promise. It is recommended that the mainstay of pharmacological rapid tranquillisation should be parenteral benzodiazepines used with due care.


[Experiences from practical guideline development--proposal of a more standardized guideline development process].
In this article, the authors of the ,,General Practitioners' Guideline for the Diagnosis and Treatment of Urinary Incontinence" describe the logical and procedural steps involved in the development process of this evidence-based GPs' guideline for the management of urinary incontinence. Specifically, the following factors have been identified as crucial for a successful primary care guideline development process: The work group (authors) should comply in size with current recommendations for successful project work teams. It is recommended that authors should belong to opposing ends of the spectrum of practical versus theoretical medicine. We argue that the integration of both practical experience and theoretical knowledge/research experience be combined in order to collate guideline recommendations that are firmly grounded in scientific evidence and both applicable and acceptable in everyday practice. Proper work on a guideline development project should only start after ensuring that the well-known theoretical requirements for sensible guidelines are met, i.e. the problem in our special focus should be widespread or of considerable economic/public health importance, be amenable to proper medical intervention, and some quality issue regarding the current handling of this problem should have been demonstrated. Subsequently, a clear logical analysis of the problem's inherent functional/logical/practical subdivisions has to be conducted. Each author is then allocated his or her fair share of the work. The next step is considered to be extremely important and consists of discovering one's "illusive correlation", i.e. inherent ideas one has on the subject without being aware of one's own bias. The proposed "trick" now consists of making the implicit bias an explicit fact in the further guideline development process. The remaining work steps build on the integration of one's preformed ideas with current, published opinion from standard textbooks, as well as existing guidelines and non-guideline recommendations on the subject; plus taking into account the practical experience gathered from interviews and "on-location-visits". This integration process is performed within a structured framework to facilitate objectivity and transparency of the entire guideline.


[Knowledge and truths about nursing: discourse of new students].
It is a study with a qualitative approach that proposes to analyze truths regimes that pass by and along Nursing as a profession, as manifested by students entering in the Graduate Course 2004/2, 2005/1 and 2005/2. The Discourse Analysis has been used as a methodological option for analyzing the data, under Michel Foucault's approaches. Three great themes have come out of such context of analysis and discussion: the traversing of gender knowledges in Nursing practice; Nursing as a knowledge made hierarchical; making as a might in Nursing's academic and professional day-by-day. Social conceptions became self evident, going through invisible knowledges that legitimate health and nursing practices, making them unquestionable.


Mechanisms of idiopathic left ventricular tachycardia.
Idiopathic left ventricular tachycardia (ILVT) differs from idiopathic right ventricular outflow tract (RVOT) tachycardia with respect to mechanism and pharmacologic sensitivity. ILVT can be categorized into three subgroups. The most prevalent form, verapamil-sensitive intrafascicular tachycardia, originates in the region of left posterior fascicle of the left bundle. This tachycardia is adenosine insensitive, demonstrates entrainment, and is thought to be due to reentry. The tachycardia is most often ablated in the region of the posteroinferior interventricular septum. A second type of ILVT is a form analogous to adenosine-sensitive RVOT tachycardia. This tachycardia appears to originate from deep within the interventricular septum and exits from the left side of the septum. This form of VT also responds to verapamil and is thought to be due to cAMP-mediated triggered activity. A third form of ILVT is propranolol sensitive. It is neither or initiated or terminated by programmed stimulation, does not terminate with verapamil, and is transiently suppressed by adenosine, responses consistent with an automatic mechanism. Recognition of the heterogeneity of ILVT and its unique characteristics should facilitate appropriate diagnosis and therapy in this group of patients.


[Unilateral sensory neuropathy of the trigeminal nerve as the leading symptom of primary Sjögren syndrome ("sicca syndrome")].
We report a case who presenting with a progressive numbness and mild hyperpathia in the second cutaneous division of the left trigeminal nerve as the leading symptom of Primary Sjögren's Syndrome. Further typical features of this autoimmune disorder are keratoconjunctivitis sicca and xerostomia. A symmetrical, predominantly sensory polyneuropathy can be revealed by sensory nerve conduction studies of the median and sural nerves. Laboratory findings mostly include elevated erythrocyte sedimentation rate, hypergammaglobulinemia and hypercomplementemia. The presence of the precipitating antinuclear antibodies SS-A and/or SS-B is pathognomonic for Sjögren's Syndrome. As long as the disease remains benign, treatment should be symptomatic. Malignant exacerbations require immunosuppressive treatment.


Evaluation of sugarcane promising clones based on the morphophysiological traits developed from fuzz.
Sugarcane is one of the critical commercial crops and principal sources of ethanol and sugar worldwide. Unfavorable conditions and poor seed setting rates hinder variety development in sugarcane. Countries like Pakistan directly import fuzz (true seed) and other propagation material from the USA, China, Brazil, etc. In this study, we imported fuzz from China, developed 29 genotypes germinating in the glasshouse, and evaluated at field conditions along with two local checks (CPF-251 and HSF-240). Morphophysiological data were recorded, including plant height (PH), cane length (CL), internodal length (IL), tiller number (TN), brix percentage (B), cane diameter (CD), chlorophyll a (Chl. a), chlorophyll b (Chl. b), and total chlorophyll (T. Chl). Results showed highly significant (p < 0.001) differences among the sugarcane accessions for all the studied traits. High broad-sense heritability (81.89% to 99.91%) was recorded for all the studied parameters. Genetic Advance (GA) ranges from 4.6% to 65.32%. The highest GA was observed for PH (65.32%), followed by CL (63.28%). Chlorophyll leaching assay was also performed at different time points (0, 50, 100, 150, and 200 min). All the genotypes showed the same leaching trend at all times, and better performing genotypes showed less leaching compared to poor performing, indicating the high amount of cutin and wax on the leaf surface. Correlation analysis showed that PH, CL, IL, and TN had significant associations. Principal components analysis (PCA) further confirms these results. Based on PCA and correlation results, PH, CL, IL, and TN can be utilized as a selection criterion for sugarcane improvement. Genotypes such as NS-4a, NS-5, NS-6, NS-8, NS-9, and NS-15 are recommended for future breeding programs related to sugarcane variety development.


Pharmacological properties of dermatan sulfate, of a low molecular weight dermatan sulfate and of two oversulfated derivatives.
The pharmacological properties of unfractionated dermatan sulfate (U-DS, mean MW 25 kd, range 12-45 kd) of a low molecular weight fraction (LMW-DS, mean MW 4 kd range 1.6-8 kd), and of 2 oversulfated derivatives (S-DS1 and S-DS2, 2 and 3.8 sulfate groups per disaccharide units) were investigated. In a purified system, LMW-DS, S-DS1 and S-DS2 were respectively 0.5, 10 and 17 times more potent than U-DS to catalyse thrombin inhibition by heparin cofactor II. Identical differences were observed for the respective anticoagulant activities (activated partial thromboplastin time and thrombin clotting time). After bolus IV injection of increasing doses the pharmacokinetic parameters of U-DS were slightly dose dependent, and the total clearance of LMW-DS was, on the average, 2 times higher. The patterns of disappearance of S-DS1 and S-DS2 were strongly dose dependent and became concave-convex, suggesting different mechanisms of clearance. After SC injection, the bioavailability was less than 50% for U-DS and at least 100% for LMW-DS. The antithrombotic activity (Wessler-thromboplastin model) of LMW-DS was 2 timer lower than that of U-DS. In contrast to their in vitro (and ex vivo) enhanced anticoagulant activities, the antithrombotic potency of S-DS1 was identical to that of U-DS, while, at the same doses S-DS2 was devoid of any activity.


Comprehensive pulmonary rehabilitation for a 90-year-old patient with intertrochanteric fracture complicated by chronic obstructive pulmonary disease: a case report.
Chronic obstructive pulmonary disease (COPD)-induced osteoporosis, myasthenia, and disequilibrium are important risk factors for hip fracture, and decreased respiratory function after hip fracture surgery can decelerate recovery of activities of daily living (ADL) in elderly patients. A 90-year-old male patient underwent an open reduction and intramedullary pinning surgery for right femoral intertrochanteric fracture. After surgery, he remained confined to bed with pain and swelling in the right lower extremity. Due to his history of COPD, he had a postoperative pulmonary infection and respiratory insufficiency. This patient received routine rehabilitation after surgery. However, severe respiratory symptoms prevented him from completing the rehabilitation procedure. Therefore, comprehensive pulmonary rehabilitation including airway clearance techniques, inspiratory resistance training, aerobic training, respiratory muscle training, and intermittent low-flow oxygen inhalation was carried out to enhance the recovery process. After 4 weeks of treatment, the patient improved from continuous oxygen inhalation to being able to complete bed resistance training without supplemental oxygen. After 8 weeks, ADL reached independence, while lower limb muscle strength, pulmonary function parameters, fatigue index, and cough efficiency were improved as compared to test values obtained before treatment. Compared with the 6-month recovery time reported in the literature for patients with hip fractures to achieve independence with basic ADLs, the recovery time of this patient was shortened to 2 months with the application of comprehensive pulmonary rehabilitation. It is feasible to carry out pulmonary rehabilitation for elderly patients after fracture surgery, but prospective clinical trials are needed to verify its efficacy.


Effect of water extract of the bark of Buchanania lanzan linn. on behaviour and chromatophores of a fresh water fish, Labeo rohita.
Fish exposed to 150 ppm and 250 ppm doses saparately, showed eratic swimming with hyper-excitability, spiralling, convulsion and mortality. However at 350 ppm dose fish became lethargic and steady at the bottom of aquarium. This behaviour appears to be due to sedative effects of fish implicating the phychoactive nature of the plant B. Ianzan. At 150 ppm to 350 ppm doses, fish scale changed from reticulate to punctate chromatophores; and treated fish when transferred to fresh water, were slowly regained to normal behaviour after 96 h exposure. Hence doses regaining from 150 ppm to 350 ppm is considered to be psychoative in nature. In higher doses 450 ppm and 550 ppm fish could survive only 76 h and 4.30 h respectively and then died indicating toxicity of plant for the said doses. It is found that scale present on its body is most suitable test system for the study of psychoactivity and toxicity of plant extracts on fish, Labeo rohita.


Central nervous system leukemia in a patient with concurrent nasopharyngeal carcinoma and acute myeloid leukaemia: A case report.
Concurrent case of nasopharyngeal carcinoma (NPC) and acute myeloid leukemia (AML) has not been reported. Here, we report a case of NPC, who was concurrently suffered from AML one mother after the NPC diagnosis. The patient was a 45-year-old male who presented with a mass on his right side neck. The patient was diagnosed with Epstein-Barr virus negative type-2 non-keratinizing carcinoma with clivus involvement and unilateral metastasis to the cervical lymph node. He was treated with one cycle of cisplatin and 69.76 Gy of concurrent external-beam radiation. Three months after completion of chemo-radiotherapy, the patient was diagnosed as acute myeloid leukemia, which achieved complete remission after one course induction chemotherapy. Two months later, however, the patient was diagnosed as central nervous system leukemia. He ultimately died of relapsed leukemia. The overall survival of the patient was 10 months. The co-occurrence of NPC and AML is rare and prognosis is poor. Radiotherapy in NPC can disrupt the blood-brain barrier, which may contribute to the pathogenesis of central nervous system leukemia. Early alert and prevention of central nervous system leukemia following radiotherapy in NPC patient is recommended.


Fosbury flop tear of the rotator cuff: diagnostic assessment with magnetic resonance arthrography.
The aim was to assess the diagnostic performance of magnetic resonance arthrography (MRA) of the shoulder for the detection of "Fosbury flop" tears. All patients undergoing arthroscopic rotator cuff repair were considered as potentially eligible for inclusion in this prospective case series. Preoperative MRAs were consecutively performed and compared with intraoperative findings being the gold standard control. Two experienced musculoskeletal radiologists, blinded to the arthroscopic findings, independently analysed all MRAs for the presence of typical signs of Fosbury flop tears. 423 patients were included. Among this group, 11 presented a Fosbury flop tear with a prevalence of 2.6%. Interobserver agreement was considered as excellent for thickened tendon, tendon stump, fluid accumulation, abnormal fibres orientationand adherences between tendon and bursa. The most sensitive and specific criterion was the tendon thickness[90.9% CI(62.3-98.4) and97.1% CI(95.0-98.3), respectively]. Conclusions: Fosbury flop tear is an uncommon condition that should be recognized to allow optimal anatomic repair. MRA is a valuable tool in making the diagnosing of this lesser recognized type of rotator cuff tear. An abnormally thickened supraspinatus tendon tear should especially raise suspicion for a Fosbury flop tear of the posterosuperior rotator cuff. Advances in knowledge: MRA is a valuable tool in making the diagnosing of Fosbury flop tears. An abnormally thickened supraspinatus tendon tear should especially raise suspicion for such lesion.


Pollens causing allergy and their monitoring by aerobiology and phenology.
Allergies caused by inhalant allergens, particularly pollens, are steadily increasing in urban centers. It is known that atmospheric pollution is strongly related to the inflammatory disease of the upper and lower airways but it is equally important in the development of sensitization towards pollens. Particulate Matter (PM), sulfur dioxide (SO2) and nitrogen dioxide (NO2) have an enhancement function on the persistence of pollens in the air, increasing the concentration and duration of pollinosis. It is therefore essential to use air quality control methods in urban centers to monitor the presence of pollen and fine dust that can drive the doctor and the patient to improve prevention, a step of primary importance in the treatment of allergies. Aerobiology and phenology are essential tools to monitor pollen production. The opportunity for the patients to use social media as information sources, including teletext, sms, mail and social networks, as well as a wide range of apps, allows to have reliable information on the air we breathe and therefore to better manage the methods of prevention at our disposal.


Fluorescence visualization of ultraviolet-sensitive cone photoreceptor development in living zebrafish.
Cone photoreceptor cells of fish retinae are arranged in a highly organized fashion. However, the molecular mechanisms underlying photoreceptor development and retinal pattern formation are largely unknown. Here we established transgenic lines of zebrafish carrying green fluorescent protein (GFP) cDNA with the 5.5-kb upstream region of the ultraviolet-sensitive cone opsin gene (SWS1). In the transgenic fish, GFP gene expression proceeded in the same spatiotemporal pattern as SWS1 in the retinae of embryos. In the adult retina, GFP expression was observed throughout the short single cone (SSC) layer where SWS1 is specifically expressed. Therefore, the transgenic fish provides an excellent genetic background to study retinal pattern formation, photoreceptor determination and differentiation, and factors regulating these processes and SSC-specific expression of SWS1.


Targeted Acid-Sensing Ion Channel Therapies for Migraine.
Acid-sensing ion channels (ASICs) are a family of ion channels, consisting of four members; ASIC1 to 4. These channels are sensitive to changes in pH and are expressed throughout the central and peripheral nervous systems-including brain, spinal cord, and sensory ganglia. They have been implicated in a number of neurological conditions such as stroke and cerebral ischemia, traumatic brain injury, and epilepsy, and more recently in migraine. Their expression within areas of interest in the brain in migraine, such as the hypothalamus and PAG, their demonstrated involvement in preclinical models of meningeal afferent signaling, and their role in cortical spreading depression (the electrophysiological correlate of migraine aura), has enhanced research interest into these channels as potential therapeutic targets in migraine. Migraine is a disorder with a paucity of both acute and preventive therapies available, in which at best 50% of patients respond to available medications, and these medications often have intolerable side effects. There is therefore a great need for therapeutic development for this disabling condition. This review will summarize the understanding of the structure and CNS expression of ASICs, the mechanisms for their potential role in nociception, recent work in migraine, and areas for future research and drug development.


Exploration of C-H Transformations of Aldehyde Hydrazones: Radical Strategies and Beyond.
The chemistry of hydrazones has gained great momentum due to their involvement throughout the evolution of organic synthesis. Herein, we discuss the tremendous developments in both the methodology and application of hydrazones. Hydrazones can be recognized not only as synthetic equivalents to aldehydes and ketones but also as versatile synthetic building blocks. Consequently, they can participate in a range of practical synthetic transformations. Furthermore, hydrazone derivatives display a broad array of biological activities and have been widely applied as pharmaceuticals. Owing to the weak directing group effect of simple aldehydes and ketones in C-H bond functionalizations, the C-H bond functionalizations of hydrazones that have been developed in the past five years represent a significant step forward. These novel transformations open a new door to a broader library of functionalized and complex small molecules. Moreover, a wide range of biologically important N-heterocycles (dihydropyrazoles, pyrazoles, indazoles, cinnolines, etc.) can be efficiently synthesized in an atom- and step-economical manner through single, double, or triple C-H bond functionalizations of hydrazones. Both radical C-H functionalizations and transition-metal-catalyzed directing-group strategies have enhanced the synthetic utility of hydrazones in the chemical community because these strategies solve the long-standing challenge of C-H functionalizations adjacent to aldehydes and ketones. We began this study based on our ongoing interest in visible-light photoredox catalysis. Visible-light photoredox catalysis has become a powerful tool in contemporary synthetic chemistry due to its remarkable advantages in sustainability and use of radical chemistry. By exploiting a photoredox-catalyzed aminyl radical polar crossover (ARPC) strategy, we successfully achieved visible-light-induced C(sp2)-H difluoroalkylation, trifluoromethylation, and perfluoroalkylation of aldehyde-derived hydrazones. This intriguing result was later applied in the C(sp2)-H amination of hydrazones and a cascade cyclization reaction for the synthesis of polycyclic compounds. Encouraged by this redox-neutral C-H functionalization of aldehyde hydrazones, we extended the oxidative C-H/P-H cross-coupling method, which represents a novel and efficient method for the synthesis of α-iminophosphine oxides. Furthermore, an elegant [3 + 2] cycloaddition of azides and aldehyde hydrazones for the synthesis of functionalized tetrazoles was advantageously developed during our investigation of the oxidative C(sp2)-H azidation of aldehyde hydrazones with TMSN3. The sequential C(sp2)-H/C(sp3)-H bond functionalization of aldehyde-derived hydrazones with simple 2,2-dibromo-1,3-dicarbonyls was achieved by employing relay photoredox catalysis, and it provides a novel method of accessing bioactive fused dihydropyrazole derivatives. The notable feature of this approach was further reflected in the formal [4 + 1] annulation of aldehyde-derived N-tetrahydroisoquinoline hydrazones with 2-bromo-1,3-dicarbonyls. To complement these radical C-H functionalization strategies, we recently applied a directing-group strategy in the Rh-catalyzed C(aldehyde)-H functionalization of aldehyde-derived hydrazones for the synthesis of distinctive and bioactive 1H-indazole scaffolds. In summary, this Account presents recent contributions to the exploration, development, mechanistic insights, and synthetic applications of C-H bond functionalizations of aldehyde hydrazones.


Biclonal immunoglobulin M dysglobulinaemia: evolving aspects in a case of primary Sjögren's syndrome.
The observation of suggestive clinical symptoms in a patient suffering from a Gougerot-Sjögren syndrome led to a search for a cryoglobulin. Unusual physico-chemical features of this cryoglobulin were discovered, using standard electrophoresis, immunoelectrophoresis, immunofixation and electroimmunotransfer. The main unusual finding was that the cryoprecipitate was made up of a biclonal IgM kappa associated to polyclonal IgG. Therefore, we suggest that this new form of cryoglobulin be classified as a subtype IIb, thus distinguishing two subtypes in the usual classification.


[The disappearance and transfer behavior of PCBs bestrewed into semi-field soil systems].
The disappearance and transfer behavior of polychlorinated biphenyl (PCBs) (the mains of penta-PCBs) at higher concentrations (400 mg/kg) bestrewed into semi-field soil systems were studied under near field conditions (semidry climate in North China). The result showed that PCBs did not lose and transfer forward below after 12 months of treatment. And after 24 months of treatment, only less than 2% of PCBs transferred vertically no more than 10 cm and PCBs concentration at treatment layers decreased 10.19% including the amount of transfer. It provides the scientific foundation for the landfill or other treatment measurements of PCBs, also gives the basic data for ecological risk assessment of PCBs and other relative compounds.


Anisotropy, segmental dynamics and polymorphism of crystalline biogenic carboxylic acids.
Carboxylic acids of the Krebs cycle possess invaluable biochemical significance. Still, there are severe gaps in the availability of thermodynamic and crystallographic data, as well as ambiguities prevailing in the literature on the thermodynamic characterization and polymorph ranking. Providing an unambiguous description of the structure, thermodynamics and polymorphism of their neat crystalline phases requires a complex multidisciplinary approach. This work presents results of an extensive investigation of the structural anisotropy of the thermal expansion and local dynamics within these crystals, obtained from a beneficial cooperation of NMR crystallography and ab initio calculations of non-covalent interactions. The observed structural anisotropy and spin-lattice relaxation times are traced to large spatial variations in the strength of molecular interactions in the crystal lattice, especially in the orientation of the hydrogen bonds. A completely resolved crystal structure for oxaloacetic acid is reported for the first time. Thanks to multi-instrumental calorimetric effort, this work clarifies phase behavior, determines third-law entropies of the crystals, and states definitive polymorph ranking for succinic and fumaric acids. These thermodynamic observations are then interpreted in terms of first-principles quasi-harmonic calculations of cohesive properties. A sophisticated model capturing electronic, thermal, and configurational-entropic effects on the crystal structure approaches captures the subtle Gibbs energy differences governing polymorph ranking for succinic and fumaric acids, representing another success story of computational chemistry.


Extravascular incidental findings in computed tomography angiography are associated with lower amputation-free survival in patients with acute lower limb ischaemia.
Emergency computed tomography angiography (CTA) is the most important imaging modality to visualize arterial occlusions in patients with acute lower limb ischaemia (ALI). Extravascular incidental findings (EVIFs) have received less attention. The aims of this study were to evaluate the incidence of EVIFs of immediate clinical relevance in patients with ALI undergoing CTA and evaluate the association between EVIFs and emergency revascularization and amputation-free survival at 1 year. Retrospective cohort study. Emergency CTA in patients with ALI between 2015 and 2018 were independently scrutinized by two senior radiologists. EVIFs were classified into immediate (category I), potential (category II) or no clinical relevance (category III). Multi-variable binary logistic regression analysis was expressed in Odds ratios (OR) with 95% confidence intervals (CI). The intra-class correlation (ICC) coefficient for EVIF category I between the raters was 0.94 (95% CI 0.92-0.96). Among 118 patients with ALI, 78 patients underwent emergency revascularization. Forty-six EVIFs (34 patients) were category I, of which 63% were found in the chest, including pleural effusion (n = 12), pneumonia (n = 8) and cardiac thrombus (n = 4). Ascites (n = 4) and cancer disease (n = 4) were other category I findings. Category I EVIFs were associated with reduced rate of emergency revascularization (OR 0.26, 95% CI 0.10-0.66) and increased rate of combined major amputation/mortality at 1 year (OR 2.9, 95% CI 1.1-8.2) in adjusted analysis. It is important to evaluate EVIFs in emergency CTA in patients with ALI since these findings are both common and associated with reduced emergency revascularization and amputation-free survival at 1 year.


O(2)-responsive chemical sensors based on hybrid xerogels that contain fluorinated precursors.
We report the development and analytical figures of merit associated with several new O(2)-responsive sensor materials. These new sensing materials are formed by sequestering the luminophore tris(4,7-diphenyl-1,10-phenanthroline)ruthenium(II) ([Ru(dpp)(3)](2+)) within hybrid xerogels that are composed of two of the following methoxysilanes: tetramethoxysilane, n-propyl-trimethoxysilane, 3,3,3-trifluoropropyl-trimethoxysilane, phenethyl-trimethoxysilane, and pentafluorophenylpropyl-trimethoxysilane. Steady-state and time-resolved luminescence measurements are used to investigate these hybrid xerogel-based sensor materials and elucidate the underlying reasons for the observed performance. The results show that many of the [Ru(dpp)(3)](2+)-doped composites form visually uniform, crack-free xerogel films that can be used to construct O(2) sensors that have linear calibration curves and excellent long-term stability. To the best of our knowledge, the [Ru(dpp)(3)](2+)-doped fluorinated hybrid xerogels also exhibit the highest O(2) sensitivity of any reported [Ru(dpp)(3)](2+)-based sensor platform.


Iron-Catalyzed Reductive Cyclization by Hydromagnesiation: A Modular Strategy Towards N-Heterocycles.
A reductive cyclization to prepare a variety of N-heterocycles, through the use of ortho-vinylanilides, is reported. The reaction is catalyzed by an inexpensive and bench-stable iron complex and generally occurs at ambient temperature. The transformation likely proceeds through hydromagnesiation of the vinyl group, and trapping of the in situ generated benzylic anion by an intramolecular electrophile to form the heterocycle. This iron-catalyzed strategy was shown to be broadly applicable and was utilized in the synthesis of substituted indoles, oxindoles and tetrahydrobenzoazepinoindolone derivatives. Mechanistic studies indicated that the reversibility of the hydride transfer step depends on the reactivity of the tethered electrophile. The synthetic utility of our approach was further demonstrated by the formal synthesis of a reported bioactive compound and a family of natural products.


Ankle Injuries in the Pediatric Emergency Department.
Ankle injuries are a common reason for presentation to the pediatric emergency department. An understanding of the anatomy of the ankle joint, the mechanism of injury, and a thorough history and physical examination can help narrow the differential diagnosis. This article will discuss the management of common ankle injuries, including ankle sprains, dislocations, and pediatric fractures, including transitional triplane and Tillaux fractures. A brief review of the literature regarding radiographic evaluation of the ankle and various ankle rules is also discussed.


Motor entropy in response to task demands and environmental information.
This experiment tested the hypothesis that human motor adaptation can be represented as the conservation of entropy across the task, organism, and environment. Healthy young individuals generated a submaximal isometric force with the index finger of their dominant hand. Subjects performed this task under different task demands (error tolerance) and environmental information (feedback frequency) conditions. In order to extend previous findings, we employ the use of approximate entropy (ApEn) to capture the temporal aspects of the variability in the isometric force and to create links to other studies of time-series in human behavior. We showed that ApEn of the force time-series, made conditional upon satisfying the task demands, decreased as the task demands were increased and the environmental information reduced. There was a compensatory interaction between task and environment on the force dynamics that could be represented by a quadratic surface, capturing 92% of the total variance. Our results show that when faced with a reduced likelihood of achieving the task goal (increased task entropy) and an environment that provides little information (increased environmental entropy), the subjects employed similar force production strategies over time, resulting in a more regular pattern.


[Gastrointestinal Complication after Lung Transplantation].
A total number of 1,787 patients have been registered in the Japan Organ Transplantation Network (JOTN), of whom 838 (46.9%) have received cadaveric lung transplantation or living-donor lobar lung transplantation since The Japanese Organ Transplant Law took effect in 1997. Subsequent to four other university hospitals( Tohoku, Kyoto, Osaka and Okayama), Fukuoka University Hospital was authorized to start lung transplantation in 2005. The survival rates after lung transplantation are lower than other solid organ transplantations not only in Japan but also around the world due to complications including infections and rejections. Between December 2005 and June 2021, 129 patients from the Fukuoka University Hospital were registered in the JOTN, and 50 underwent lung transplantation( five living-donor lobar lung transplantations and 45 cadaveric lung transplantations). Herein, we report our single-center experience of lung transplant program and an overview of the observed gastrointestinal complications associated with lung transplantation at our center.


Pressure-induced novel ZrN4 semiconductor materials with high dielectric constants: a first-principles study.
In addition to Zr3N4 and ZrN2 compounds, zirconium nitrides with a rich family of phases always exhibit metal phases. By employing an evolutionary algorithm approach and first-principles calculations, we predicted seven novel semiconductor phases for the ZrN4 system at 0-150 GPa. Through calculating phonon dispersions, we identified four dynamically stable semiconductor structures under ambient pressure, namely, α-P1̄, β-P1̄, γ-P1̄, and β-P1 (with bandgaps of 1.03 eV, 1.10 eV, 2.33 eV, and 1.49 eV calculated using the HSE06 hybrid density functional, respectively). The calculated work functions and dielectric functions show that the four dynamically stable semiconductor structures are all high dielectric constant (high-k) materials, among which the β-P1̄ phase has the largest static dielectric constant (3.9 times that of SiO2). Furthermore, we explored band structures using the HSE06 functional and density of states (DOS) and the response of bandgaps to pressure using the PBE functional for the four new semiconductor configurations. The results show that the bandgap responses of the four structures exhibit significant differences when hydrostatic pressure is applied from 0 to 150 GPa.


[Effect of treatment with Triton X-100 on DNA integrity and DNA:RNA: protein ratio of rat liver nuclei].
A procedure is described that gives clean nuclei with intact DNA from a rat liver cell suspension. Cytoplasmic contamination is removed by successive treatments with a non ionic detergent, Triton X-100 (0.75%, v/v). We found that with ratios DNA:RNA: protein of 1:0.09:3.29 (2 Triton X-100 steps) the integrity of DNA is preserved: further decrease in RNA and protein content (3 Triton X-100 steps) causes DNA breakage, probably because of extraction of nuclear proteins. In order to estimate DNA integrity, its viscosity was determined by the use of a new oscillating crucible viscometer; this method makes possible the evaluation of extremely small levels of DNA damage as that induced by 0.067 mg/kg of DMNA injected i.p.


The economic burden of epilepsy in Bhutan.
To assess the economic impact of epilepsy in Bhutan, a lower-middle-income country with a universal health care system, but with limited access to neurological care. A cross-sectional survey was conducted of patients with epilepsy at the Jigme Dorji Wangchuk National Referral Hospital from January to August 2016. Data were collected on clinical features, cost of care, impact of epilepsy on school or work and household economic status of participants and matched comparisons (a sibling or neighbour from a household without epilepsy). A total of 172 individuals were included in the study (130 adults and 42 children). One-third of adults and 20 (48%) children had seizures at least once per month. Mean direct out-of-pocket cost for epilepsy care was 6054 Bhutanese Ngultrum (BTN; 91 USD) per year, of which transportation formed the greatest portion (53%). Direct costs of epilepsy were an average of 3.2% of annual household income. Adults missed 6.8 (standard deviation [SD]: 9.0) days of work or school per year on average, and children missed 18.6 (SD: 34.7) days of school. Among adults, 23 (18%) abandoned employment or school because of epilepsy; seven children (18%) stopped school because of epilepsy. Households with a person with epilepsy had a lower monthly per-person income (6434 BTN) than comparison households without epilepsy (8892 BTN; P = 0.027). In Bhutan, despite universal health care services, households of people with epilepsy face a significant economic burden. With many adults and children unable to attend school or work, epilepsy causes a major disruption to individuals' livelihoods.


Sub-nanometric High-Entropy Alloy Cluster: Hydrogen Spillover Driven Synthesis on CeO2 and Structural Reversibility.
High-entropy alloy (HEA) nanoparticles (NPs) have attracted significant attention as promising catalysts owing to the various unique synergistic effects originating from the nanometer-scale, near-equimolar mixing of five or more components to produce single-phase solid solutions. However, the study of sub-nanometer HEA clusters having sizes of less than 1 nm remains incomplete despite the possibility of novel functions related to borderline molecular states with discrete quantum energy levels. The present work demonstrates the synthesis of CeO2 nanorods (CeO2-NRs) on which sub-nanometer CoNiCuZnPd HEA clusters were formed with the aid of a pronounced hydrogen spillover effect on readily reducible CeO2 (110) facets. The CoNiCuZnPd HEA sub-nanoclusters exhibited higher activity during the reduction of NO by H2 even at low temperatures compared with the corresponding monometallic catalysts. These clusters also showed a unique structural reversibility in response to repeated exposure to oxidative/reductive conditions, based on the sacrificial oxidation of the non-noble metals. Both experimental and theoretical analyses established that multielement mixing in quantum-sized regions endowed the HEA clusters with entirely novel catalytic properties.


Altered metabolism in the ex vivo remnant kidney. II. Effects of metabolic inhibitors and dietary protein.
To understand further the contribution of heightened net sodium reabsorption (TNa+) and other nontransport processes to increased and altered metabolic activity of the rat remnant kidney (RK), isolated RK and normal kidneys (NK) were perfused with and without metabolic inhibitors and following 4 weeks of low (12%)- or high (40%)-protein diet. 3-Mercaptopicolinate (200 microM) and 2-deoxyglucose (200 microM) reduced glucose production and consumption, respectively, without altering oxygen consumption (QO2). Ouabain reduced TNa+ and QO2 in NK but not RK, and increased glucose consumption in RK (by 67%, p < 0.02, n = 12) and NK (by 54%, p < 0.05, n = 12). Raising perfusate pH by 0.3 U to 7.65 increased glucose production in RK but not NK and reduced TNa+ in NK but not RK. Dietary protein restriction reduced QO2 (2.18 +/- 0.29 vs. 4.13 +/- 0.20 mumol-1 x min-1 x g-1, p < 0.001), TNa+ (8.74 +/- 4.39 vs. 38.83 +/- 8.32, p < 0.01) and ammoniagenesis (0-30 min, 0.16 +/- 0.05 vs. 0.32 +/- 0.10, p < 0.05) in RK, but not NK. In summary: (1) responses to ouabain and alkalosis, but not other metabolic inhibitors, were quite distinct in remnant versus normal kidneys, and (2) protein restriction limited sodium-transport-dependent and -independent hypermetabolism in RK.


[Cancer epigenetics].
Knowledge regarding molecular events of cancer development has been rapidly accumulated during the last decade. The discovery of tumor suppressor gene-silencing by aberrant promoter CpG island hypermethylation and histone-directed chromatin remodeling has led epigenetics to its recognition as an important alternative mechanism for carcinogenesis. Epigenetics does not involve changes in nucleotide sequences, but it affects on genetic composition in many ways. Cancer cells integratively co-opt genetic and epigenetic mechanisms to acquire different aspects of carcinogenetic phenotypes. Since epigenetic changes can be reversed with relative ease, the research of cancer epigenetics provides great potential for new therapeutic regimens.


The Management of Women's Health Care by Internists With a Focus on the Utility of Ultrasound.
Adult women require routine care for the acute and chronic health problems found in both sexes, and they require specialized care for women's health problems, including disease prevention, disease screening, and disease management. Internists should direct primary care and participate in specialized care and to the extent possible follow guidelines published by various professional organizations. They should understand the use of ultrasound in breast cancer screening, the management of pregnancy, and other gynecologic problems, including vaginal bleeding, pelvic pain, and investigation for pelvic malignancy. Finally, all management decisions need discussions on the potential benefit or harm in each step of a woman's care with an emphasis on personal preferences.


Human parvovirus B19 infections: routine diagnosis by a new nested polymerase chain reaction assay.
A nested primer PCR assay was developed to detect human parvovirus B19 in various clinical specimens in a routine diagnostic laboratory. Under optimized conditions the highly specific assay had a sensitivity of less than 10 genome units. For practical reasons, however, this sensitivity was adjusted to 10-100 virus genomes in diagnostic applications. Using clinical specimens from 200 patients with suspected B19 infection, nested PCR was shown to have important diagnostic advantages over the detection of B19 specific antibodies. The data suggest that on the basis of serological data as obtained with currently available test systems a considerable proportion of B19 infections would be misdiagnosed. Examples for the usefulness of the PCR assay in routine diagnosis are given.


Sociodemographic and clinical determinants of quality of life in urban population of Poland.
The aim of the study was to assess quality of life (QL) of residents of Polish urban area and analyze the influence of selected sociodemographic and clinical variables on their QL. The study revealed a very high level of reported problems, especially regarding pain and anxiety. The mean subjective assessment of health state was poor in comparison with results obtained in other (usually western) countries. Presence of major risk factors of cardiovascular diseases had an important impact on QL. Elevated blood pressure and unsatisfactory level of physical activity were the strongest factors deteriorating QL in the studied population. There is a need for implementing effective interventions in the society, especially in the area of prevention and management of hypertension and sedentary lifestyle.


Sex differences in hearing: Probing the role of estrogen signaling.
Hearing loss is the most common form of sensory impairment in humans, with an anticipated rise in incidence as the result of recreational noise exposures. Hearing loss is also the second most common health issue afflicting military veterans. Currently, there are no approved therapeutics to treat sensorineural hearing loss in humans. While hearing loss affects both men and women, sexual dimorphism is documented with respect to peripheral and central auditory physiology, as well as susceptibility to age-related and noise-induced hearing loss. Physiological differences between the sexes are often hormone-driven, and an increasing body of literature demonstrates that the hormone estrogen and its related signaling pathways may in part, modulate the aforementioned differences in hearing. From a mechanistic perspective, understanding the underpinnings of the hormonal modulation of hearing may lead to the development of therapeutics for age related and noise induced hearing loss. Here the authors review a number of studies that range from human populations to animal models, which have begun to provide a framework for understanding the functional role of estrogen signaling in hearing, particularly in normal and aberrant peripheral auditory physiology.


Reductions in Corpus Callosum Volume Partially Mediate Effects of Prenatal Alcohol Exposure on IQ.
Disproportionate volume reductions in the basal ganglia, corpus callosum (CC) and hippocampus have been reported in children with prenatal alcohol exposure (PAE). However, few studies have investigated these reductions in high prevalence communities, such as the Western Cape Province of South Africa, and only one study made use of manual tracing, the gold standard of volumetric analysis. The present study examined the effects of PAE on subcortical neuroanatomy using manual tracing and the relation of volumetric reductions in these regions to IQ and performance on the California Verbal Learning Test-Children's Version (CVLT-C), a list learning task sensitive to PAE. High-resolution T1-weighted images were acquired, using a sequence optimized for morphometric neuroanatomical analysis, on a Siemens 3T Allegra MRI scanner from 71 right-handed, 9- to 11-year-old children [9 fetal alcohol syndrome (FAS), 19 partial FAS (PFAS), 24 non-syndromal heavily exposed (HE) and 19 non-exposed controls]. Frequency of maternal drinking was ascertained prospectively during pregnancy using timeline follow-back interviews. PAE was examined in relation to volumes of the CC and left and right caudate nuclei, nucleus accumbens and hippocampi. All structures were manually traced using Multitracer. Higher levels of PAE were associated with reductions in CC volume after adjustment for TIV. Although the effect of PAE on CC was confounded with smoking and lead exposure, additional analyses showed that it was not accounted for by these exposures. Amongst dysmorphic children, smaller CC was associated with poorer IQ and CVLT-C scores and statistically mediated the effect of PAE on IQ. In addition, higher levels of PAE were associated with bilateral volume reductions in caudate nuclei and hippocampi, effects that remained significant after control for TIV, child sex and age, socioeconomic status, maternal smoking during pregnancy, and childhood lead exposure. These data confirm previous findings showing that PAE is associated with decreases in subcortical volumes and is the first study to show that decreases in callosal volume may play a role in fetal alcohol-related impairment in cognitive function seen in childhood.


Atypical renal onset and involvement in primary antiphospholipid syndrome in a child.
A case of primary antiphospholipid syndrome (APS) with renal involvement in a 10-year-old child is reported. The peculiarity of the case resided not only in the apparent "primary" occurrence of APS in the pediatric age, but also in the involvement of the kidney. The renal picture in the case described consisted of a focal proliferative glomerulonephritis, without any sign of glomerular thrombosis. We conclude that this should lead to a consideration of primary APS in the differential diagnosis of nephropathies, also in childhood.


Restless legs syndrome induced by quetiapine: report of seven cases and review of the literature.
We report on seven cases of restless legs syndrome (RLS) in patients treated with quetiapine. Small doses (50-250 mg at bedtime) provoked RLS in a dose-dependent way. Most patients suffered from an affective disorder and all were treated concomitantly with antidepressants. A search of the literature revealed a further nine cases of RLS concerning quetiapine, also afflicting only patients with affective disorders. Quetiapine seems to carry a special risk for RLS in this sort of patient. Possible causes for this concurrence are discussed.


Preclinical evaluation of sodium cellulose sulfate (Ushercell) as a contraceptive antimicrobial agent.
The spread of sexually transmitted infections (STIs) and limited methods for control of pregnancies presents high risks to the reproductive health of women. Methods controlled by women and directed toward disease prevention and contraception are needed. We report on preclinical studies of the biological properties of sodium cellulose sulfate (Ushercell) currently being developed for use as a topical contraceptive antimicrobial agent. Ushercell was evaluated with tests designed to identify its contraceptive and antimicrobial properties. Ushercell inhibits hyaluronidase (reversible; IC50 = 1.7 mg/mL), impairs sperm penetration of cervical mucus (approximately 70% inhibition at 1 mg/mL), and acts as a stimulus for acrosomal loss (IC50 = 52 ng/mL). It prevents conception in rabbits when added to spermatozoa (approximately 95% inhibition at 1 mg/mL) or when vaginally applied (complete contraception by 45 mg) before insemination. However, up to 50 mg/mL, Ushercell does not irreversibly immobilize spermatozoa, suggesting that Ushercell is not cytotoxic. Ushercell has a broad spectrum of antimicrobial activity in vitro. Inhibited microbes include human immunodeficiency viruses (different laboratory strains and clinical isolates; IC50 values range from 3 to 78 microg/mL), herpes viruses, HSV-1 (IC50 = 59 ng/mL) and HSV-2 (lC50 = 24 ng/mL), Neisseria gonorrhoeae (IC50 = 2 microg/mL), and Chlamydia trachomatis (IC50 = 78 microg/mL). In contrast, Ushercell does not inhibit growth of beneficial vaginal bacteria, Lactobacillus gasseri, at 5 mg/mL. These results suggest that the antimicrobial effects of Ushercell are selective, and not likely mediated by nonspecific cytotoxic mechanisms. These data provide the basis for further clinical development of Ushercell as a vaginal agent to prevent unplanned pregnancy and STIs.


Co-representation of others' task constraints in joint action.
Previous research has demonstrated that humans tend to represent each other's tasks even if no interpersonal coordination is required. The present study asked whether coactors in a joint action rely on task co-representation to achieve temporal coordination even if this implies increased movement effort for an unconstrained actor. Pairs of participants performed reaching movements back and forth between two targets, with the aim of synchronizing their landing times. One of the participants needed to move over an obstacle while the other had no obstacle. The results of four experiments showed that the participant without obstacle moved as if an obstacle was obstructing her way. Further amplifying the demands on interpersonal coordination led to a significant increase of this effect, indicating that unconstrained actors represented their coactor's task constraint and adjusted their own actions accordingly, particularly under high coordination demands. The findings also showed that unconstrained actors represented the object property constraining their coactor's movement rather than parameters of this movement. We conclude that joint action partners rely on task co-representation to achieve temporal coordination in a task with asymmetric task constraints. (PsycINFO Database Record


Fast analysis of proteins by isoelectric focusing performed in capillary array detected with concentration gradient imaging system.
Isoelectric focusing of several protein samples is performed simultaneously in an array of 2-4 short capillaries (4-10 cm long). The separated proteins are detected by either an on-line concentration gradient imaging detection system, or a single point concentration gradient detector which requires a mobilization step following the focusing process. The application of the capillary array increases the throughput of the capillary isoelectric focusing (CIEF) technique, and makes the technique comparable in sample throughput to the gel slab isoelectric focusing technique, but with much faster speed of separation and quantitation. The analysis is completed in 2-3 min with the imaging detection system, which is about 100 times faster than the conventional gel slab isoelectric focusing and 10 times faster compared to conventional CIEF. The resolution of the separation is 0.02 pH units or better. All separated proteins in the capillary array are detected by the universal concentration gradient detector, which eliminates the need for sample derivatization. The concentration limit of detection for the inexpensive instrument described in this work is about 30 micrograms/mL and can be reduced by using higher quality components in the system, such as a more stable laser, higher optical quality capillaries and a faster computer A/D board. The sample consumption is 400 nL for the 4 cm long, 100 microns ID square capillary. The isoelectric point (pI) values of the samples can be directly determined without internal pI markers from their positions inside the capillary after focusing when the imaging detection system is used.


Ventilation rates in recently constructed U.S. school classrooms.
Low ventilation rates (VRs) in schools have been associated with absenteeism, poorer academic performance, and teacher dissatisfaction. We measured VRs in 37 recently constructed or renovated and mechanically ventilated U.S. schools, including LEED and EnergyStar-certified buildings, using CO2 and the steady-state, build-up, decay, and transient mass balance methods. The transient mass balance method better matched conditions (specifically, changes in occupancy) and minimized biases seen in the other methods. During the school day, air change rates (ACRs) averaged 2.0±1.3 hour-1 , and only 22% of classrooms met recommended minimum ventilation rates. HVAC systems were shut off at the school day close, and ACRs dropped to 0.21±0.19 hour-1 . VRs did not differ by building type, although cost-cutting and comfort measures resulted in low VRs and potentially impaired IAQ. VRs were lower in schools that used unit ventilators or radiant heating, in smaller schools and in larger classrooms. The steady-state, build-up, and decay methods had significant limitations and biases, showing the need to confirm that these methods are appropriate. Findings highlight the need to increase VRs and to ensure that energy saving and comfort measures do not compromise ventilation and IAQ.


Intervention of the Syndrome-Position Point Selection Method on Idiopathic Tinnitus of Phlegm-Fire Stagnation Pattern: A Randomized Controlled Study.
To investigate the clinical effect of the syndrome-position point selection method on the intervention of idiopathic tinnitus of the phlegm-fire stagnation pattern. One hundred patients with idiopathic tinnitus of phlegm-fire stagnation pattern who met the inclusion criteria were randomized into the treatment group and the control group by the random number table method, with 50 cases in each group. The treatment group (syndrome-position point selection method) was treated with acupuncture at the corresponding acupoints for tinnitus and associated symptoms and the corresponding acupoints located in Wernicke's area of scalp projection, while the control group (traditional acupuncture method) was treated with the combination of acupuncture points with the most frequent occurrence in the tinnitus research literature for acupuncture treatment. Both groups received acupuncture twice a week for 5 weeks. The efficacy was evaluated before and after treatment with the Tinnitus Severity Inventory (TSI), Sleep Spiegel Questionnaire, Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS). The 100 patients with idiopathic tinnitus of phlegm-fire stagnation pattern completed 5 weeks of clinical treatment and a month of follow-up with no loss of patients and no adverse event reports. Three patients recovered with the disappearance of the tinnitus symptoms in the treatment group after 5 weeks of treatment. After 5 weeks of treatment, obvious differences between the two groups were observed in the TSI scores (P < 0.05) and the Spiegel scores, with a better Spiegel score in the treatment group than in the control group (P < 0.05). Compared with the control group, the depression (SDS score) and anxiety (SAS score) of tinnitus patients in the treatment group were markedly improved (P < 0.05). In line with the principle of symptomatic treatment and based on the modern imaging data, the syndrome-position point selection method is more accurate and effective compared with the traditional acupoint selection method, which significantly improves the symptoms, sleep quality, and psychological state of patients with idiopathic tinnitus of the phlegm-fire stagnation pattern.


Cardiac contractile proteins and sarcoplasmic reticulum in hearts of rats trained by running.
Rats were trained with two running protocols previously demonstrated to result in enhanced cardiac performance. Control groups included free-eating sedentary animals and food-restricted animals in which the body weights were the same as the runners. Calcium binding by isolated sarcoplasmic reticulum (SR) was slightly but significantly increased in SR from runners at low but not high calcium concentrations at 15 s and 1 min. Calcium uptake in the presence of 1 mM oxalate was increased in SR from runners. Actomyosin ATPase activity was increased by 10% (P less than 0.001) with one running protocol but not with the other. Myosin Ca2+ ATPase activity and actin-activated ATPase activity were also slightly increased in hearts of runners. In food-restricted cardiac actomyosin ATPase was significantly decreased. Actomyosin ATPase activity was found to be normal in hearts of sedentary animals subjected to water immersion without exercise. Therefore, physical training of rats by running, which produces a cardiac mechanical advantage similar to training by swimming, is not accompanied by cardiac biochemical changes of the same magnitude as in the hearts of swimmers.


[Vascular access in elderly: AVF versus CVC].
The characteristics of patients on dialysis have changed significantly in the last years. Aging and comorbidity are the most important aspects of this change. Vascular access problems are frequent in elderly people and contribute to the increased morbidity and mortality. Arteriovenous fistula (AVF) remains the preferred method but may be difficult or unadvisable in older patients because of a short life expectancy, poor vasculature or poor cardiac function. In fact, increasing use of CVC has been reported in recent studies. Psychological and quality of life-related aspects should also be taken into account when scheduling vascular access in older patients: from this point of view CVC may be a good alternative to an aggressive surgical policy. Decreasing CVC-related complications is feasible through the consistent application of basic rules; the center effect may be relevant in this context. However, the use of CVC remains a kind of double-edged sword: even in older people preferring it over AVF is justified only if good results can be guaranteed. The final choice will have to be based on a multidisciplinary approach and careful assessment of resources.